Risk of Liver and Other Types of Cancer in Patients
With Cirrhosis: A Nationwide Cohort Study in Denmark
HENRIK TOFT SØRENSEN,1 SØREN FRIIS,2 JØRGEN H. OLSEN,2 ANE MARIE THULSTRUP,3 LENE MELLEMKJÆR,2 MARTHA LINET,4
DIMITRIOS TRICHOPOULOS,5 HENDRIK VILSTRUP,1 AND JØRN OLSEN3
Cancer risk in patients with cirrhosis could be modified
by factors such as changes in hormonal levels, impaired
metabolism of carcinogens, or alteration of immunological
status. We investigated the risk of liver and various forms of
cancer in patients with cirrhosis in a follow-up study. We
identified 11,605 1-year survivors of cirrhosis from the files
of the Danish National Registry of Patients (NRP) from
1977 to 1989. Occurrence of cancer through 1993 was
determined by linkage to the Danish Cancer Registry. For
comparison, the expected number of cancer cases was
estimated from national age-, sex-, and site-specific inci-
dence rates. Overall, 1,447 cancers were diagnosed among
the study subjects, as compared with 708.1 expected, to
yield a standardized incidence ratio (SIR) of 2.0 (95% CI:
1.9 to 2.2). In all diagnostic subgroups of cirrhosis, the risk
of primary liver cancer, mainly hepatocellular carcinoma,
was markedly elevated, with 245 observed cases and an
overall 36-fold elevated risk (59.9-fold elevated for hepato-
cellular carcinoma and 10-fold for cholangiocarcinoma).
Substantial and persistent excesses during follow-up were
seen for all types of cancer associated with tobacco and
alcohol habits (cancer of the lung, larynx, buccal cavity,
pharynx, pancreas, urinary bladder, and kidney), while
moderate excesses were seen for cancers of the colon and
breast. The latter, however, were not complemented by any
decrease in the risk of prostate cancer (SIR: 1.0; 95% CI: 0.7
to 1.3). A slightly increased risk was seen for testis cancer,
but disappeared after 10 years. We found evidence of an
increased risk for liver and several extrahepatic cancers in
patients with cirrhosis. Although part of this increase is
Abbreviations: NRP, National Registry of Patients; ICD, International Classification of
Diseases; SIR, standardized incidence ratio.
From the 1Department of Medicine V, Aarhus University Hospital, Aarhus, Denmark;
2The Danish Cancer Society, Division for Cancer Epidemiology, Copenhagen, Denmark;
3The Danish Epidemiology Science Centre at the Department of Epidemiology and
Social Medicine, Aarhus University, Aarhus, Denmark; 4National Cancer Institute,
Radiation Epidemiology Branch, Rockville, MD; and 5Department of Epidemiology
and the Harvard Center for Cancer Prevention, Harvard School of Public Health,
Boston, MA.
Received January 8, 1998; accepted May 4, 1998.
Supported by the Oncologic Research Unit at Aalborg Hospital, by the Ebba and Aksel
Sjølin Foundation, by research grant MAO N01-CP-85639-04 from the National Cancer
Institute, Bethesda, MD, and The Danish Medical Research Council (grant 9700766).
The activities of the Danish Epidemiology Science Centre are financed by a grant from
the Danish National Research Foundation.
Address reprint requests to: Dr. Henrik Toft Sørensen, The Danish Epidemiology
Science Centre at the Department of Epidemiology and Social Medicine, Aarhus
University, DK-8000 Aarhus C, Denmark. Fax: 45-86-13-15-80.
Copyright r 1998 by the American Association for the Study of Liver Diseases.
0270-9139/98/2804-0004$3.00/0
921
likely attributable to alcohol and tobacco consumption, our
study opens up the possibility that cirrhosis plays a role in
the carcinogenesis of types of cancer other than liver cancer.
(HEPATOLOGY 1998;28:921-925.)
The incidence of liver cancer varies from 100 in 100,000
per year in certain parts of Africa and Asia to less than 4 in
100,000 per year in most parts of Europe and North
America.1 The incidence of various forms of cirrhosis in
Denmark varies from 9 per million person-years for primary
biliary cirrhosis to 137 per million person-years for alcoholic
cirrhosis.2 In general, the incidences of liver cancer and
cirrhosis follow similar patterns of variation, because these
two diseases share etiologic factors. Important causes of liver
cancer are alcohol and hepatitis B and C viruses,3-11 which
likely act indirectly through cirrhosis.3
Whether cirrhosis is a risk factor for cancer at sites other
than the liver has not been well investigated, except for
patients with primary biliary cirrhosis.7,11-14 Changes in the
metabolism of carcinogens or hormones could, however,
affect cancer risk. It is known that cirrhosis induces changes
in estrogen metabolism,15 and male patients with cirrhosis
have hyperestrogenism, which may lead to gynecomastia and
testis atrophy. Recent studies in women indicate that cirrhosis
is associated with menstrual irregularity, increased frequency
of spontaneous abortion, and early menopause.16 Moreover,
the liver plays a central role in the metabolism of lipid and
water-soluble drugs and other chemicals, and patients with
cirrhosis have also been reported to experience alterations in
immune functions and risk of infections.17
To examine the risk of liver cancer and extrahepatic
cancers in patients with cirrhosis, we conducted a cohort
study using nationwide registries.
PATIENTS AND METHODS
The Danish National Registry of Patients (NRP) contains informa-
tion on virtually all hospital admissions in Denmark (population:
5.2 million) since 1977.18 Each admission record includes the
personal identification number that is unique to every Danish
resident, dates of admission, dates of discharge, and up to 20
discharge diagnoses. Diagnoses are classified according to the
Danish version of the International Classification of Diseases, 8th
edition (ICD-8).19 Persons were enrolled in the study if they had
been discharged with alcoholic cirrhosis (ICD-8 5 571.09), primary
biliary cirrhosis (571.90), nonspecified cirrhosis (571.92), chronic
hepatitis (571.93), or ‘‘other types of cirrhosis, alcoholism not
indicated’’ (571.99) at least once during the years 1977 to 1989.
Cirrhosis was considered as a whole, but also as four separate types,
largely following the ICD-8 codes given above, except that nonspeci-
fied cirrhosis and cirrhosis, alcoholism not indicated, were merged
922 SØRENSEN ET AL.
into one group termed ‘‘nonspecified cirrhosis’’ (571.92 and 571.99).
If a patient had been discharged with more than one cirrhosis
diagnosis, a prioritized order of diagnoses determined to which
group the patient was assigned: 1) alcoholic, 2) primary biliary
cirrhosis, 3) chronic hepatitis, and 4) nonspecified cirrhosis. Accord-
ingly, those persons with alcoholic cirrhosis entered this category
independently of whether they had any other cirrhosis diagnosis.
Furthermore, cirrhosis patients with a diagnosis of alcoholism
(ICD-8 5 303) at any time from 1977 to 1989 were always referred
to as the alcoholic group, no matter which cirrhosis code was
registered.
All members of the study cohort were linked through their
personal identification number to the nationwide Danish Cancer
Registry, which was initiated in 1943 and which has an almost
complete coverage of incident cancers in the country.20 The Cancer
Registry receives notifications of malignant and related diseases
from hospital departments at the time of diagnosis, and if changes in
the initial diagnosis occur. In addition, reports are received from
pathology departments and departments of forensic medicine,
giving the results of autopsies of cancer patients. Also, cases first
diagnosed at autopsy, i.e., as an incidental finding, are included in
the Registry’s material. This information is supplemented by a
review of the files of the NRP and of all death certificates. Cancers
were classified according to the modified Danish version of the
International Classification of Diseases, 7th revision (ICD-7)20 and
since January 1, 1978, also according to the International Classifica-
tion of Diseases for Oncology (ICD-O).20 For liver cancers, the latter
classification includes a subgrouping of cases according to tumor
morphology, i.e., hepatocellular carcinomas, cholangiocarcinomas,
mixed hepatocellular-cholangiocarcinomas and hemangiosarcomas.
Liver cancers without specification for morphological type were
only included in the site-specific cancer analysis if they were
explicitly notified as ‘‘primary liver cancer.’’
The follow-up period for cancer occurrence began at the date of
discharge with cirrhosis from the hospital, irrespective of type, and
ended at the date of death or December 31, 1993, whichever came
first. Dates of death were obtained through linkage with the
nationwide Cause of Death Registry.
Statistics. The number of cancer cases observed among study
subjects was compared with the number of cases expected on the
basis of rates from the Danish Cancer Registry, and the standardized
incidence ratio (SIR) was calculated as the ratio of the observed to
the expected number of cancer cases. The expected number of
cancers was calculated by multiplying the number of person-years of
study subjects by the site- and morphology-specific national inci-
dence rates of each sex in 5-year age groups and calendar periods of
observation. The statistical methods used assumed that the observed
number of cases in any specific category followed a Poisson
distribution. Tests of significance and confidence interval for the SIR
were calculated based on Byar’s approximation; exact confidence
limits were used if the observed number of cancers was less than
10.21
To avoid selection bias that might have been introduced by the
entry of study subjects with cirrhosis and concurrent cancer, we
computed risk estimates for cancer excluding observed and ex-
pected cancers during the first year of follow-up after discharge from
TABLE 1. Descriptive Characteristics of 11,605 1-Year Survivors With Cirrhosis in Denmark, 1977-1989
Alcoholic
Characteristics Men Women
No. of patients 5,079 2,086
Person-years at risk 28,801 12,508
Average age at discharge with cirrhosis (yr) 51.8 52.5
Mean follow-up time (yr) 5.7 6.0
HEPATOLOGY October 1998
the hospital for cirrhosis. Of the 18,358 patients with cirrhosis
notified to the NRP, 6,753 (37%) died within the first year of
follow-up, leaving 11,605 for cancer risk analysis.
RESULTS
Table 1 shows characteristics of the 11,605 patients with
cirrhosis included in the risk analysis. In both sexes com-
bined, alcoholic cirrhosis was the most frequent specific
subtype in Denmark (62%), followed by cirrhosis from
chronic hepatitis (15%), and primary biliary cirrhosis (3%).
In 21% of cases, the origin of cirrhosis remained nonspeci-
fied. There were more men than women among patients with
alcoholic cirrhosis, whereas more women than men had
primary biliary cirrhosis and cirrhosis from chronic hepatitis
(Table 1).
Over the entire follow-up period, 1,447 cancers were
diagnosed; 708.1 were expected in the combined cohort,
which yields an SIR of 2.0 (95% CI: 1.9-2.2) (Table 2). The
risk for liver cancer was exceptionally high, with 245
observed cases against 6.8 expected (SIR: 36; 95% CI: 32-41).
The excess risk was most pronounced for hepatocellular
carcinoma. Significant excesses were seen for cancer related
to tobacco, and alcohol habits and for cancer of the stomach
(SIR: 1.9; n 5 40) and colon (SIR: 1.5; n 5 82); this pattern
was evident in both sexes combined as well as separately
(Table 2). A slight increase in risk was observed for hormone-
related cancers, in particular breast cancer in women and
testis cancer in men. The number of observed prostate
cancers was as expected. There were 20% more cases of
nonmelanoma skin cancer than expected, which was exclu-
sively a result of an excess among women, whereas there was
a reduction in the number of malignant melanomas and of
cancers of the brain/nervous system.
The risk for liver cancer was most pronounced during early
follow-up (1-4 years; SIR: 42.8; 95% CI: 36.1-50) compared
with late follow-up, though it remained high (101 years; SIR:
28.8; 95% CI: 19.6-40.9) (data not shown). The excess risks
for tobacco- and alcohol-related cancers, kidney, breast and
colon cancer, also persisted during late follow-up, but ex-
cesses of testis and stomach cancer were not present after 10
years.
Table 3 shows that the SIR for all cancers combined was
increased in all types of cirrhosis, though only slightly in
patients with primary biliary cirrhosis. The SIR of liver cancer
was markedly increased in all subcohorts, ranging from 44.8
(alcoholic cirrhosis) to 18.5 (primary biliary cirrhosis). The
cancer pattern was quite similar in alcoholic cirrhosis,
chronic hepatitis, and nonspecified cirrhosis, with elevated
risks of tobacco- and alcohol-related cancers, testicular
cancer, stomach cancer, and colon cancer. An exception was
the risk of breast cancer, which was increased only in
Type of Cirrhosis
Primary Biliary Chronic Hepatitis Nonspecified
Men Women Men Women Men Women
57 263 712 978 1,210 1,220
374 1,777 5,466 7,494 6,666 7,208
57.9 60.5 43.4 55.1 57.5 61.7
6.5 6.7 7.7 7.7 5.5 5.9
HEPATOLOGY Vol. 28, No. 4, 1998 SØRENSEN ET AL. 923

TABLE 2. Observed and Expected Numbers and SIR of Cancer in 11,605 Patients With Cirrhosis
Both Sexes Men Women

Cancer Site Observed Expected SIR 95% CI Observed SIR Observed SIR

All malignant neoplasms 1,447 708.1 2.0 1.9-2.2 896 2.2* 551 1.8*
Liver (primary) 245 6.8 36.0 31.6-40.8 182 40.2* 63 27.8*
Hepatocellular carcinoma 199 3.3 59.9 51.8-68.8 152 59.5* 47 97.8*
Cholangiocarcinoma 21 2.1 10.0 6.2-15.2 13 11.4* 8 8.3*
Other and unspecified morphologies 25 1.4 18.3 11.8-27.0 17 20.6* 8 14.8*
Tobacco-related sites, total 356 188.6 1.9 1.7-2.1 244 1.8* 112 2.2*
Lung 207 102.5 2.0 1.8-2.3 143 1.9* 64 2.5*
Urinary bladder 62 45.8 1.4 1.0-1.7 47 1.3 15 1.7
Kidney 45 20.1 2.2 1.6-3.0 27 2.1* 18 2.5*
Pancreas 42 20.1 2.1 1.5-2.8 27 2.4* 15 1.7
Alcohol-related sites, total† 241 31.3 7.7 6.8-8.7 173 7.0* 68 10.5*
Buccal cavity and pharynx 143 15.5 9.2 7.8-10.8 96 8.1* 47 12.9*
Esophagus 54 7.2 7.5 5.6-9.8 41 7.4* 13 7.7*
Larynx 44 8.5 5.2 3.8-6.9 36 4.9* 8 7.1*
Hormone-related sites, total 151 135.4 1.1 0.9-1.3 42 1.0 109 1.2*
Breast 83 63.7 1.3 1.0-1.6 2 3.2 81 1.3*
Endometrium 14 16.5 0.9 0.5-1.4 — — 14 0.9
Ovary 14 13.7 1.0 0.6-1.7 — — 14 1.0
Prostate 40 41.6 1.0 0.7-1.3 40 1.0 — —
Other sites, total‡ 454 346.0 1.3 1.2-1.4 255 2.0* 199 1.3*
Stomach 40 21.3 1.9 1.3-2.6 28 2.0* 12 1.7
Colon 82 55.4 1.5 1.2-1.8 42 1.5* 40 1.5*
Rectum 40 32.4 1.2 0.9-1.7 23 1.1 17 1.5
Gallbladder and biliary tract 8 6.0 1.3 0.6-2.6 3 1.3 5 1.4
Cervix uteri 11 10.4 1.1 0.5-1.9 — — 11 1.1
Testis 8 3.5 2.3 1.0-4.5 8 2.3 — —
Melanoma 8 15.2 0.5 0.2-1.0 2 0.3* 6 0.8
Nonmelanoma skin 120 100.0 1.2 1.0-1.4 62 1.0 58 1.4*
Brain and nervous system 9 17.2 0.5 0.2-1.0 5 0.5 4 0.6
Thyroid 4 2.2 1.8 0.5-4.6 3 3.4 1 0.7
Non–Hodgkin’s lymphoma 19 14.9 1.3 0.8-2.0 12 1.4 7 1.2
Leukemia 20 15.8 1.3 0.8-2.0 13 1.3 7 1.3
NOTE. First years of follow-up excluded.
*P , .05.
†Liver not included; sites also influenced by tobacco.
‡Not all sites shown.

alcoholic and nonspecified cirrhosis. Although the small size
of the subcohort of primary biliary cirrhosis reduced the
ability to detect risk deviations, there seemed to be a
somewhat different cancer pattern among these patients;
apart from liver cancer, only cancer of the colon was seen in
an excess that reached a significant level (Table 3).
DISCUSSION
The study confirmed that patients with cirrhosis have a
considerably increased risk of primary liver cancer, mainly
hepatocellular carcinoma, irrespective of the specific underly-
ing cause of the cirrhosis. Our finding of a higher risk of liver
cancer in alcoholic cirrhosis than in any other type of
cirrhosis may suggest either a direct effect of alcohol on liver
carcinogenesis or induction of a more severe type of cirrhosis
carrying a higher risk of liver cancer, or both.
There is a strong association between alcohol intake,
elevated liver enzymes, and smoking habits in the Danish
population,22 and the markedly increased risks for tobacco-
related cancer sites found in all cirrhosis patients except
primary biliary cirrhosis were probably caused by excessive
use of tobacco products. The increased risks of cancer of the
stomach and large bowel may be more difficult to explain by
confounding, although stomach cancer has recently been
included in the group of tobacco-related cancers.23 Alcohol
consumption has been associated with an increased risk of
rectal cancer,24,25 and Naveau et al.26 studied the effects of
alcoholism and cirrhosis and found that alcoholics were three
times more likely than nonalcoholics to have colon adenoma-
tous polyps, controlling for cirrhosis. The same study showed
that the prevalence of colon adenomatous polyps was over
two times higher in patients with cirrhosis than in those
without cirrhosis, after controlling for alcoholism. A meta-
analysis based on 27 studies showed that for consumption of
two alcoholic beverages daily, the average, relative risk of
colorectal cancer was 1.1 (95% CI: 1.05-1.14).27 However,
because the association was small, it was concluded that the
findings regarding a causal role of alcohol were inconclusive.
The increased risk of breast cancer observed in patients
with alcoholic and nonspecified cirrhosis, but not in chronic
hepatitis, indicates that the excess is to some degree related to
alcohol intake.28 Most patients with clinical cirrhosis have
increased endogenous estrogen levels,29,30 but the moderate
size of the breast cancer finding, and the absence of an
association with chronic hepatitis, suggests that these hor-
monal changes have very little effect on breast cancer risk.
This is in line with the observation of no excess of prostate
cancer. It has been hypothesized for this male type of cancer
924 SØRENSEN ET AL. HEPATOLOGY October 1998

TABLE 3. Observed and Expected Numbers and SIR of Selected Cancer Sites in Different Types of Cirrhosis
Alcoholic Primary Biliary Chronic Hepatitis Nonspecified

Cancer Site Observed SIR 95% CI Observed SIR 95% CI Observed SIR 95% CI Observed SIR 95% CI

All malignant neoplasms 877 2.2 2.1-2.4 36 1.4 1.0-1.9 187 1.7 1.4-1.9 347 2.0 1.8-2.2
Liver (primary) 173 44.8 38.4-52.0 4 18.5 5.0-48.0 23 23.1 14.6-35.0 45 26.0 19.0-35.0
Hepatocellular carcinoma 142 70.6 59.5-83.2 4 47.0 12.6-120.2 18 42.7 25.2-67.3 35 43.4 30.3-60.4
Cholangiocarcinoma 17 15.3 8.9-24.5 0 — — 0 — — 4 7.2 1.9-18.3
Other and unspecified morphology 14 19.0 10.4-31.8 0 — — 5 23.0 7.4-53.8 6 16.6 6.0-36.0
Tobacco-related sites 210 1.8 1.6-2.1 8 1.5 0.7-3.0 42 1.7 1.2-2.3 96 2.2 1.8-2.7
Lung 135 2.1 1.8-2.5 1 0.4 0.0-2.0 19 1.5 0.9-2.4 52 2.3 1.7-3.0
Urinary bladder 32 1.1 0.8-1.6 3 2.8 0.6-8.1 9 1.6 0.7-3.1 18 1.7 1.0-2.6
Kidney 26 2.2 1.5-3.3 2 3.0 0.3-10.7 8 2.7 1.1-5.3 9 1.8 0.8-3.5
Pancreas 17 1.6 0.9-2.6 2 2.6 0.3-9.5 6 1.8 0.7-3.9 17 3.1 1.8-5.0
Alcohol-related sites 193 9.6 8.3-11.0 1 1.4 0.0-7.6 13 3.5 1.9-6.0 34 5.1 3.5-7.1
Buccal cavity and pharynx 115 11.6 9.6-14.0 0 — — 8 4.2 1.8-8.2 20 6.0 3.6-9.2
Esophagus 40 9.0 6.4-12.3 1 5.4 0.1-30 1 1.1 0.0-6.1 12 7.2 3.7-12.5
Larynx 38 6.5 4.6-9.0 0 — — 4 4.7 1.3-11.9 2 1.2 0.1-4.3
Hormone-related sites* 81 1.3 1.0-1.6 5 0.7 0.2-1.7 20 0.8 0.5-1.2 45 1.4 1.0-1.8
Breast 44 1.6 1.2-2.2 4 0.9 0.3-2.4 11 0.7 0.4-1.3 24 1.4 0.9-2.1
Other sites, total* 220 1.1 1.0-1.3 18 1.5 0.9-2.3 89 1.6 1.3-2.0 127 1.4 1.2-1.7
Stomach 16 1.4 0.8-2.2 1 1.6 0.0-8.6 10 3.2 1.5-5.8 13 2.3 1.2-3.9
Colon 43 1.5 1.1-2.1 6 2.7 1.0-5.8 15 1.5 0.9-2.5 18 1.2 0.7-1.8
Nonmelanoma 60 1.1 0.8-1.4 2 0.6 0.1-2.0 25 1.6 1.0-2.3 33 1.3 0.9-1.8
Testis 5 2.2 0.8-5.1 0 — — 2 2.7 0.0-9.9 1 2.2 0.0-12.4
NOTE. First year of follow-up excluded.
*Not all sites shown.

that cirrhosis patients have a reduced risk, again because of
the disturbances in female hormones.31-33 However, the
overall increased risk of testis cancers could be a result of the
induced estrogen exposure.29
In contrast to other types of cirrhosis, less is known about
the risk of hepatocellular carcinoma in primary biliary
cirrhosis. The previous studies of patients with primary
biliary cirrhosis have given conflicting cancer findings.3,7,9,11-
14,34,35 An increased risk of liver cancer has been reported in
some studies,9,11 but not in others.3,12,35 We found a statisti-
cally significant increase in the risk of liver cancer, higher
than in a recent large population-based study from Sweden
that reported a nonsignificant relative risk of 2.9.7 However,
our estimate relied on only four cases. We could not confirm
the previously reported excess risk for the development of
breast cancer in patients with primary biliary cirrhosis.12,13,33
A limitation of our study is the lack of information on
diagnostic criteria and potential confounding factors. A
previous study indicated high data validity of the cirrhosis
diagnosis in the NRP, but some misclassification between the
different types of cirrhosis probably exists, particularly be-
tween alcoholic and nonspecified cirrhosis.36 Therefore, we
also searched for diagnoses of alcoholism in the NRP for
those not registered with alcoholic cirrhosis to reduce this
misclassification. The subcohorts of chronic hepatitis and
nonspecified cirrhosis are likely to include an overrepresenta-
tion of alcoholic patients relative to the general population as
indicated by the increased risk for other alcohol-related
cancers; however, these groups do not contain the same
proportion of alcoholic patients as the subgroup of alcoholic
cirrhosis. Misclassification of alcoholic cirrhosis may bias
estimates across the different types of cirrhosis. The sex ratio
and follow-up time in patients with chronic hepatitis and
primary biliary cirrhosis indicate, however, that misclassifica-
tion must be of minor importance in these groups. Denmark
is a very-low-incidence area for infectious hepatitis A, B, and
C,37 and patients with autoimmune hepatitis account for a
high proportion of the patients in the chronic hepatitis group.
In the Danish population, approximately 100 cases of hepati-
tis A and B are registered per year, and less than 80 are cases of
hepatitis C. The high frequency of hepatitis B virus and
hepatitis C virus infections among individuals with alcoholic
liver diseases and alcohol-associated hepatocellular carci-
noma in some countries has led to the suggestion that these
viruses may be implicated in the pathogenesis of hepatocellu-
lar carcinoma.38 However, these infections are rare in Den-
mark. A comprehensive screening of blood donors in Den-
mark has shown a prevalence of less than 0.04%,39 so it is not
likely that hepatitis infections play an important role in the
pathogenesis of hepatocellular carcinoma in the present
study.
The clearest finding of the present study was the excessive
risk of liver cancer found in all cirrhosis patients independent
of the type of cirrhosis. Thus, cirrhosis seems to be an
essential step in the induction of liver cancer. The hormonal
and immune changes in cirrhosis did not affect the incidence
of hormone cancers and cancers related to immunosuppres-
sion to any considerable degree. The elevated risk for breast
cancer in alcoholic cirrhosis could be caused by a direct effect
of alcohol rather than the elevated estrogen level. Cirrhosis
patients experienced risk increase for many other cancers,
but several are heavily influenced by alcohol and tobacco use.
Acknowledgment: The authors thank Anne Marie E. I.
Larsen at the Division for Cancer Epidemiology for computer
assistance.
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